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This study was undertaken to determine whether an effective antianginal treatment without tolerance development can be carried out with intermittent nitrate administration on a regimen with a single daily dose of 120 mg isosorbide dinitrate (ISDN) in sustained-release form (SR), as well as whether the concomitant administration of 100 mg atenolol or 100 mg atenolol and 20 mg nifedipine renders an additive antiischemic effect. In two independently performed investigations, the duration of action of a single dose of 120 mg ISDN SR was assessed after its initial administration in addition to the anti-ischemic effect during long-term treatment, each according to a randomized, double-blind, crossover, placebo-controlled protocol in a total of 15 patients with angiographically-documented coronary artery disease, stable angina pectoris and reproducible ST-segment depression during exercise. The test phases of four weeks each were separated by one week placebo phases. After completion of the study, for a further eight weeks, 120 mg ISDN SR was given together with 100 mg atenolol in the morning. Exercise testing was carried out after four weeks of treatment in a control period before and at two hours after administration of 120 mg ISDN SR with 100 mg atenolol as well as after another four weeks in a control period before and after concomitant administration of 120 mg ISDN SR, 100 mg atenolol and 20 mg nifedipine in sustained release form.(ABSTRACT TRUNCATED AT 250 WORDS)

Nisoldipine (Bay K5552), a newly-developed dehydropyridine derivative with calcium antagonistic properties, was found to have a duration of action twice as long as its parent compound, nifedipine, in laboratory experiments. To evaluate the anti-ischemic potency and duration of action, the effects of 10 mg nisoldipine after acute administration and at the end of three weeks of treatment with 10 mg twice daily were compared with those of 120 mg verapamil three times daily in a double-blind, randomized, crossover, placebo-controlled study. In twelve patients with angiographically-documented coronary artery disease and stable exertional angina pectoris, bicycle ergometry was performed before and at three and seven hours after medication on the first and 21st days of the three respective treatment phases. The control value at 8 a.m. on the 21st day corresponded with the ten-hour value on the 20th day of treatment. Between the three treatment phases, there was a one-week wash-out period during which the patients received placebo three times daily. At the time of the ergometric studies, blood was drawn for determination of verapamil plasma concentrations and, additionally, each patient recorded anginal attacks and nitrate consumption. Analysis was carried out for ST-segment depression in each patient at the highest comparable workload achieved in all treatment phases, the time to onset of 1 mm ST-segment depression as well as the response of the heart rate, systolic arterial blood pressure and the heart rate-blood pressure double-product both at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrendipine is a newly-developed calcium channel blocker derived from the dehydropyridine series which, according to experimental studies, affects marked dilation of the peripheral and coronary vessels. As compared with the parent compound nifedipine, nitrendipine exhibits a clearly more prolonged elimination half-time. This study was designed to evaluate the antihypertensive efficacy, in particular, with respect to the duration of action as well as the anti-ischemic effectiveness with a protocol encompassing as many factors as possible. In 13 patients with angiographically-documented coronary artery disease and elevated blood pressure at rest and/or during exercise, on two days separated by a three-day washout period, we investigated the effects of 20 mg nitrendipine, as compared with placebo, in a double-blind, randomized, crossover study. The systolic and diastolic arterial blood pressure as well as the heart rate were recorded prior to, at two, five, eight and twelve hours after medication and the blood pressure only at 24 hours. Blood pressure and heart rate were assessed during active standing at two hours, passive tilt at 2 1/2 hours and, together with analysis of the ST segments, before and during semisupine bicycle ergometry performed at three hours after tablet administration.(ABSTRACT TRUNCATED AT 250 WORDS)